3-氯-2-丙烯酸 | 625-40-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-氯-2-丙烯酸
• 英文名称: 3-chloroacrylic acid
• 英文别名: cis-3-chloro acrylic acid；(Z)-3-chloroacrylicacid；3-chloroprop-2-enoic acid
• CAS: 625-40-1
• 化学式: C₃H₃ClO₂
• mdl: MFCD00004368
• 分子量: 106.509
• InChiKey: MHMUCYJKZUZMNJ-UHFFFAOYSA-N

物化性质

• 熔点：
  94 °C
• 沸点：
  192.3±13.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2916190090

反应信息

• 作为反应物：
  描述：

  3-氯-2-丙烯酸 、 4-(4-氨基苯基磺酰基)哌嗪-1-羧酸叔丁酯 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 异丁酰胺 为溶剂， 反应 1.0h， 以5%的产率得到4-[4-(3-(Z)-chloroacryloylamino)benzenesulfonyl]piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] TRANSGLUTAMINASE TG2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  [FR] INHIBITEURS DE TRANSGLUTAMINASE TG2, COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本文提供了某些化合物和药学上可接受的盐。还提供了包括至少一种化合物或其中的药学上可接受的盐以及一种或多种药学上可接受的载体的药物组合物。描述了治疗对转谷氨酰胺酶TG2活性抑制产生响应的患有某些疾病状态的患者的方法。这些疾病状态包括神经退行性疾病，如亨廷顿病。还描述了治疗方法，包括单独给予至少一种化合物或其中的药学上可接受的盐，或者将至少一种化合物或其中的药学上可接受的盐与一种或多种其他治疗剂结合给予。

  公开号：

  WO2011060321A1

文献信息

• Substituted 3-cyano quinolines
  申请人：American Cyanamid Company

  公开号：US06002008A1

  公开（公告）日：1999-12-14

  This invention provides compounds having the formula: ##STR1## wherein: X is cycloalkyl which may be optionally substituted; or is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally substituted; n is 0-1; Y is --NH--, --O--, --S--, or --NR--; R is alkyl of 1-6 carbon atoms; R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are each, independently, hydrogen, halogen, alkyl, alkenyl, alkynyl, alkenyloxy, alkynyloxy, hydroxymethyl, halomethyl, alkanoyloxy, alkenoyloxy, alkynoyloxy, alkanoyloxymethyl, alkenoyloxymethyl, alkynoyloxymethyl, alkoxymethyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylsulfonamido, alkenylsulfonamido, alkynylsulfonamido, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy, carboalkyl, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino, alkylamino, dialkylamino, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, phenylamino, benzylamino, ##STR2## R.sub.5 is alkyl which may be optionally substituted, or phenyl which may be optionally substituted; R.sub.6 is hydrogen, alkyl, or alkenyl; R.sub.7 is chloro or bromo R.sub.8 is hydrogen, alkyl, aminoalkyl, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, N-cycloalkylaminoalkyl, N-cycloalkyl-N-alkylaminoalkyl, N,N-dicycloalkylaminoalkyl, morpholino-N-alkyl, piperidino-N-alkyl, N-alkyl-piperidino-N-alkyl, azacycloalkyl-N-alkyl, hydroxyalkyl, alkoxyalkyl, carboxy, carboalkoxy, phenyl, carboalkyl+, chloro, fluoro, or bromo; Z is amino, hydroxy, alkoxy, alkylamino, dialkylamino, morpholino, piperazino, N-alkylpiperazino, or pyrrolidino; m=1-4,q=1-3, and p=0-3; any of the substituents R.sub.1, R.sub.2, R.sub.3, or R.sub.4 that are located on contiguous carbon atoms can together be the divalent radical --O--C(R.sub.8).sub.2 --O--; or a pharmaceutically acceptable salt thereof with the proviso that when Y is --NH--, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are hydrogen, and n is 0, X is not 2-methylphenyl, which are inhibitors of protein tyrosine kinase.

  这项发明提供了具有以下结构的化合物：##STR1## 其中：X是环烷基，可以选择性地被取代；或者是吡啶基、嘧啶基或苯环；其中吡啶基、嘧啶基或苯环可以选择性地被取代；n为0-1；Y为--NH--、--O--、--S--或--NR--；R为1-6个碳原子的烷基；R.sub.1、R.sub.2、R.sub.3和R.sub.4分别独立地是氢、卤素、烷基、烯基、炔基、烯氧基、炔氧基、羟甲基、卤甲基、烷酰氧基、烯酰氧基、炔酰氧基、烷酰氧甲基、烯酰氧甲基、炔酰氧甲基、烷氧甲基、烷氧基、烷基硫、烷基亚砜基、烷基磺酰基、烷基磺酰胺基、烯基磺酰胺基、炔基磺酰胺基、羟基、三氟甲基、氰基、硝基、羧基、羧基烷氧基、羧基烷基、苯氧基、苯基、噻吩氧基、苄基、氨基、羟氨基、烷氧氨基、烷基氨基、二烷基氨基、氨基烷基、N-烷基氨基烷基、N,N-二烷基氨基烷基、苯基氨基、苄氨基、##STR2## R.sub.5是可以选择性取代的烷基，或者是可以选择性取代的苯基；R.sub.6是氢、烷基或烯基；R.sub.7是氯或溴；R.sub.8是氢、烷基、氨基烷基、N-烷基氨基烷基、N,N-二烷基氨基烷基、N-环烷基氨基烷基、N-环烷基-N-烷基氨基烷基、N,N-二环烷基氨基烷基、吗啉-N-烷基、哌啶-N-烷基、N-烷基-哌啶-N-烷基、氮杂环烷基-N-烷基、羟基烷基、烷氧基烷基、羧基、羧基烷氧基、苯基、羧基+、氯、氟或溴；Z是氨基、羟基、烷氧基、烷基氨基、二烷基氨基、吗啉基、哌嗪基、N-烷基哌嗪基或吡咯烷基；m=1-4，q=1-3，p=0-3；任何位于相邻碳原子上的R.sub.1、R.sub.2、R.sub.3或R.sub.4取代基可以共同形成二价基团--O--C(R.sub.8).sub.2 --O--；或其药学上可接受的盐，但当Y为--NH--时，R.sub.1、R.sub.2、R.sub.3和R.sub.4为氢，n为0时，X不是2-甲基苯基，这些化合物是蛋白酪氨酸激酶的抑制剂。
• Method of treating or inhibiting colonic polyps
  申请人：American Cyanamid Company

  公开号：US06384051B1

  公开（公告）日：2002-05-07

  This invention provides a method of treating or inhibiting colonic polyps which comprises providing a compound of formula 1 wherein: R1, R2, R3, R4, X, Y, and n are as defined hereinbefore, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种治疗或抑制结肠息肉的方法，包括提供如下公式1的化合物： 其中： R1、R2、R3、R4、X、Y和n如前文所定义，或其药用可接受的盐。
• USE OF CYANOQUINOLINES FOR TREATING OR INHIBITING COLONIC POLYPS
  申请人：Wyeth Holdings Corporation

  公开号：EP1263503B1

  公开（公告）日：2005-11-02
• Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease
  作者：Michael E. Prime、Ole A. Andersen、John J. Barker、Mark A. Brooks、Robert K. Y. Cheng、Ian Toogood-Johnson、Stephen M. Courtney、Frederick A. Brookfield、Christopher J. Yarnold、Richard W. Marston、Peter D. Johnson、Siw F. Johnsen、Jordan J. Palfrey、Darshan Vaidya、Sayeh Erfan、Osamu Ichihara、Brunella Felicetti、Shilpa Palan、Anna Pedret-Dunn、Sabine Schaertl、Ina Sternberger、Andreas Ebneth、Andreas Scheel、Dirk Winkler、Leticia Toledo-Sherman、Maria Beconi、Douglas Macdonald、Ignacio Muñoz-Sanjuan、Celia Dominguez、John Wityak

  DOI：10.1021/jm201310y

  日期：2012.2.9

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.
• [EN] TRANSGLUTAMINASE TG2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE TRANSGLUTAMINASE TG2, COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：CHDI INC

  公开号：WO2011060321A1

  公开（公告）日：2011-05-19

  Certain compounds and pharmaceutically acceptable salts are provided herein. Also provided are pharmaceutical compositions comprising at least one compound or pharmaceutically acceptable salt therein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain disease states responsive to the inhibition of transglutaminase TG2 activity are described. These disease states include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound or pharmaceutically acceptable salt thereof as a single active agent or administering at least one compound or pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents.

  本文提供了某些化合物和药学上可接受的盐。还提供了包括至少一种化合物或其中的药学上可接受的盐以及一种或多种药学上可接受的载体的药物组合物。描述了治疗对转谷氨酰胺酶TG2活性抑制产生响应的患有某些疾病状态的患者的方法。这些疾病状态包括神经退行性疾病，如亨廷顿病。还描述了治疗方法，包括单独给予至少一种化合物或其中的药学上可接受的盐，或者将至少一种化合物或其中的药学上可接受的盐与一种或多种其他治疗剂结合给予。